Quercetin protects against sepsis-associated encephalopathy by inhibiting microglia-neuron crosstalk via the CXCL2/CXCR2 signaling pathway.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is a common brain lesion associated with severe sepsis, for which ferroptosis is a key driving factor. Thus, suppressing ferroptosis may be an effective strategy for treating SAE. Quercetin (QUE) is a natural flavonoid with antioxidant and anti-inflammatory properties. However, its role on ferroptosis in SAE remains unclear. PURPOSE: This study aimed to investigate the mechanism underlying the therapeutic effect of QUE on cecal ligation perforation (CLP)-induced SAE. METHODS: In vivo and in vitro SAE models were established using CLP and lipopolysaccharide (LPS), respectively. Both models underwent pre-treatment with QUE. RESULTS: QUE attenuated CLP-induced symptoms, including temperature changes, neurological severity scores, learning and memory dysfunction, inflammatory cytokine release, and microglia activation in SAE mice, and inhibited LPS-induced microglia recruitment and chemotaxis. Bioinformatics analysis revealed that the C-X-C motif chemokine ligand 2 (CXCL2)/C-X-C motif chemokine receptor 2 (CXCR2) axis may play a key role in QUE-mediated protection against SAE. Moreover, QUE significantly inhibited LPS-induced CXCL2 up-regulation and protein secretion from microglia. Recombinant mouse-derived CXCL2 (rmCXCL2) promoted inflammatory cytokine secretion, NF-κB/NLRP3 signaling activation, and microglia recruitment and chemotaxis. Furthermore, rmCXCL2 induced ferroptosis in mouse hippocampal neurons, as evidenced by elevated malondialdehyde levels, decreased glutathione levels, excessive iron uptake, and altered ferroptosis-related protein expression. The CXCR2 antagonist SB225002 effectively reversed the effects of rmCXCL2. Importantly, in vivo experiments further demonstrated that the therapeutic effect of QUE on SAE was inhibited by rmCXCL2. CONCLUSION: This study demonstrates that CXCL2 secreted by activated microglia mediates microglia self-activation and induces hippocampal neuronal ferroptosis via CXCR2 and that QUE exerts neuroprotective effects on SAE by blocking interactions between microglia and neurons via CXCL2/CXCR2 pathway inhibition.

Ring-Opening Sulfonylation of Cyclic Sulfonium Salts with Sodium Sulfinates under Transition-Metal- and Additive-Free Conditions.

Incorporating a sulfonyl group into parent molecules has been shown to effectively improve their synthetic applications and bioactivities. In this study, we present a straightforward and practical approach for the ring-opening reaction of alkenyl-aryl sulfonium salts with sodium sulfinates to produce a range of sulfur-containing alkyl sulfones. This method offers the benefits of mild reaction conditions, easily accessible raw materials, wide substrate applicability, good functional group compatibility, and operational simplicity. Importantly, the resulting products can be readily converted into sulfoxides, sulfones, sulfoximines, and some heterocyclic compounds.

Anti-hypertensive effect and potential mechanism of gastrodia-uncaria granules based on network pharmacology and experimental validation.

Hypertension has become a major contributor to the morbidity and mortality of cardiovascular diseases worldwide. Despite the evidence of the anti-hypertensive effect of gastrodia-uncaria granules (GUG) in hypertensive patients, little is known about its potential therapeutic targets as well as the underlying mechanism. GUG components were sourced from TCMSP and HERB, with bioactive ingredients screened. Hypertension-related targets were gathered from DisGeNET, OMIM, GeneCards, CTD, and GEO. The STRING database constructed a protein-protein interaction network, visualized by Cytoscape 3.7.1. Core targets were analyzed via GO and KEGG using R package ClusterProfiler. Molecular docking with AutodockVina 1.2.2 revealed favorable binding affinities. In vivo studies on hypertensive mice and rats validated network pharmacology findings. GUG yielded 228 active ingredients and 1190 targets, intersecting with 373 hypertension-related genes. PPI network analysis identified five core genes: AKT1, TNF-α, GAPDH, IL-6, and ALB. Top enriched GO terms and KEGG pathways associated with the anti-hypertensive properties of GUG were documented. Molecular docking indicated stable binding of core components to targets. In vivo study showed that GUG could improve vascular relaxation, alleviate vascular remodeling, and lower blood pressure in hypertensive animal models possibly through inhibiting inflammatory factors such as AKT1, mTOR, and CCND1. Integrated network pharmacology and in vivo experiment showed that GUG may exert anti-hypertensive effects by inhibiting inflammation response, which provides some clues for understanding the effect and mechanisms of GUG in the treatment of hypertension.

Improving iPSC Differentiation Using a Nanodot Platform.

Differentiation of induced pluripotent stem cells (iPSCs) is an extremely complex process that has proven difficult to study. In this research, we utilized nanotopography to elucidate details regarding iPSC differentiation by developing a nanodot platform consisting of nanodot arrays of increasing diameter. Subjecting iPSCs cultured on the nanodot platform to a cardiomyocyte (CM) differentiation protocol revealed several significant gene expression profiles that were associated with poor differentiation. The observed expression trends were used to select existing small-molecule drugs capable of modulating differentiation efficiency. BRD K98 was repurposed to inhibit CM differentiation, while iPSCs treated with NSC-663284, carmofur, and KPT-330 all exhibited significant increases in not only CM marker expression but also spontaneous beating, suggesting improved CM differentiation. In addition, quantitative polymerase chain reaction was performed to determine the gene regulation responsible for modulating differentiation efficiency. Multiple genes involved in extracellular matrix remodeling were correlated with a CM differentiation efficiency, while genes involved in the cell cycle exhibited contrasting expression trends that warrant further studies. The results suggest that expression profiles determined via short time-series expression miner analysis of nanodot-cultured iPSC differentiation can not only reveal drugs capable of enhancing differentiation efficiency but also highlight crucial sets of genes related to processes such as extracellular matrix remodeling and the cell cycle that can be targeted for further investigation. Our findings confirm that the nanodot platform can be used to reveal complex mechanisms behind iPSC differentiation and could be an indispensable tool for optimizing iPSC technology for clinical applications.

91-month follow-up of solitary punctate chorioretinitis in a Chinese patient.

BACKGROUND: Solitary Punctate Chorioretinitis (SPC) is a recently identified form of punctate inner choroidopathy (PIC) characterized by a single lesion in the fovea of the macula. Previous studies with a maximum follow-up of 48 months were insufficient. Our review uncovered a case sustained for 91 months. CASE PRESENTATION: A 28-year-old young woman experienced with sudden visual loss in her right eye. Comprehensive examinations, including assessment of best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, noncontact tonometry, fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), optical coherence tomography angiography (OCTA), perimetry, and microperimetry, were conducted. Over 91 months, the lesion slightly enlarged, remained yellow-white and punctate, and stayed in the central macula of the posterior pole. OCT images depicted subsidence in the inner nuclear layer (INL), the outer plexiform layer (OPL), photoreceptor layer, and disruption of the external limiting membrane (ELM), ellipsoid zone, and retinal pigment epithelium (RPE)/Bruch's membrane complex. Retinal herniation, focal choroidal excavation (FCE), and abnormal vessels in the choriocapillaris were noted. At the slab of the choriocapillaris, OCTA demonstrated that the lesion resembled a linear vascular structure, distinct from the structure of normal choriocapillaris. This confirmed the lesion as an abnormal vascular formation. FAF revealed a punctate hypo-autofluorescence lesion and abnormal hyper-autofluorescence near the optic disc and macula. FFA demonstrated a punctate hyper-fluorescent lesion inferotemporal to the fovea. The vascular structure remained stable without fluid exudation on OCT images, hence anti-vascular endothelial growth factor (anti-VEGF) treatment was not administered. Visual acuity improved from counting fingers to 0.07 in 52 days, reached 0.6 after 15 months, remained at 0.6 from 56 to 80 months, and returned to 0.8 after 91 months, although accompanied by local scotomas. The lesion pattern slightly enlarged without scarring. CONCLUSIONS: Throughout long-term follow-up, we had long suspected the presence of choroidal neovascularization (CNV) and found the FCE in the last visit. Eventually, we concluded that SPC could potentially constitute a distinct subtype of PIC. The patient received no treatment, and vision recovered to 0.8. If CNV is suspected in SPC, anti-VEGF treatment may not be necessary without activity on OCT, but close monitoring is essential.

Ts2O mediated deoxygenative C2-dithiocarbamation of quinoline N-oxides with CS2 and amines.

A general, efficient and practical protocol for Ts2O promoted deoxygenative dithiocarbamation of quinoline N-oxides with in situ generated dithiocarbamic acids from CS2 and amines is reported. The reaction proceeded well under transition-metal free conditions to obtain a variety of novel quinoline-dithiocarbamate compounds with wide functional group tolerance and good to high yields.

The effect of acupuncture on gastrointestinal recovery after abdominal surgery: a narrative review from clinical trials.

Abdominal surgery is a critical surgery, with more and more attention being paid to postoperative life quality and associated complications in recent years. Among these complications, postoperative gastrointestinal dysfunction is the most common complication of abdominal surgery. Acupuncture therapy is a treatment approach based on the Traditional Chinese Medicine (TCM) theory, and its feasibility in aiding the gastrointestinal recovery after abdominal surgery is supported by both TCM theory and animal experiments. A lot of clinical research has been conducted to evaluate its efficacy, albeit with limitations and at preliminary stages. Moreover, intervention timing, acupoint selection, and patient benefits should also be considered in clinical practices. This article summarizes the progress of clinical research on acupuncture therapy in the gastrointestinal recovery after abdominal surgery, and discusses related issues and operations, with the aim to provide new insights and prospect for the incorporation of acupuncture into the Enhanced Recovery After Surgery (ERAS) protocol.

Integrating quantitative microbiological risk assessment and disability-adjusted life years to evaluate the effects of urbanization on health risks for river recreationists.

Urban rivers provide an excellent opportunity for water recreation. This study probabilistically assessed health risks associated with water recreation in urban rivers in the Bitan Scenic Area, Taiwan, by employing quantitative microbial risk assessment and disability-adjusted life years (DALYs). Moreover, the effects of urbanization on the health risks of river recreation induced by waterborne pathogenic Escherichia coli (E. coli) were investigated. First, data on river E. coli levels were collected in both the Bitan Scenic Area and the upstream river section, and model parameters were obtained through a questionnaire administered to river recreationists. Monte Carlo simulation was then employed to address parameter uncertainty. Finally, DALYs were calculated to quantify the cumulative effects in terms of potential life lost and years lived with disability. The results indicated that the 90 % confidence intervals for the disease burden (DB) were 0.2-74.1 × 10-6, 0.01-94.0 × 10-6, and 0.3-128.9 × 10-6 DALY per person per year (pppy) for canoeing, swimming, and fishing, respectively, in the Bitan Scenic Area. Furthermore, urbanization near the Bitan Scenic Area approximately doubled the DB risks to river recreationists in upstream rural areas. At the 95th percentile, the DB risks exceeded the tolerances recommended by the World Health Organization (1 × 10-6) or U.S. Environmental Protection Agency (1 × 10-4). The findings suggest that the simultaneous implementation of effluent sewer systems and best management practices can reduce health risks to river recreationists by at least half, reducing the DALY levels below 1 × 10-4 or even 1 × 10-5 pppy.

Efficient synthesis of SCF3-containing 3-alkenylquinoxalinones via three-component radical cascade reaction.

An efficient and practical method for the synthesis of 3-alkenylquinoxalinones containing the SCF3 group has been readily developed through a three-component radical cascade reaction involving quinoxalinones, alkynes and AgSCF3. The reaction was found to be compatible with a variety of substrates and exhibited a high functional group tolerance and complete E-selectivity. The preliminary study suggests the involvement of a SCF3 radical in the transformation.

Therapeutic application of circular RNA aptamers in a mouse model of psoriasis.

Efforts to advance RNA aptamers as a new therapeutic modality have been limited by their susceptibility to degradation and immunogenicity. In a previous study, we demonstrated synthesized short double-stranded region-containing circular RNAs (ds-cRNAs) with minimal immunogenicity targeted to dsRNA-activated protein kinase R (PKR). Here we test the therapeutic potential of ds-cRNAs in a mouse model of imiquimod-induced psoriasis. We find that genetic supplementation of ds-cRNAs leads to inhibition of PKR, resulting in alleviation of downstream interferon-α and dsRNA signals and attenuation of psoriasis phenotypes. Delivery of ds-cRNAs by lipid nanoparticles to the spleen attenuates PKR activity in examined splenocytes, resulting in reduced epidermal thickness. These findings suggest that ds-cRNAs represent a promising approach to mitigate excessive PKR activation for therapeutic purposes.

Survival outcome and optimal candidates of primary tumor resection for patients with metastatic medullary thyroid cancer.

CONTEXT: Medullary thyroid cancer (MTC) often exhibits aggressive growth with distant organ metastasis, leading to poor survival. OBJECTIVE: The question of whether primary tumor resection (PTR) is beneficial for patients with metastatic MTC remains a subject of debate. In this study, we evaluated the prognostic significance of organ-specific metastases and the number of metastatic organs in these patients, and we also conducted an analysis to determine the therapeutic value of PTR in managing this rare malignancy. MATERIALS AND METHODS: Patients initially diagnosed with metastatic MTC were identified within the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable Cox proportional hazards regression models were performed to identify survival predictors. Survival outcomes were calculated using the Kaplan-Meier method and compared using the log-rank tests. RESULTS: A total of 186 patients with metastatic MTC at initial diagnosis from 2010 to 2020 were included. Bone, lung and liver were the most common metastatic organs. Patients with brain metastasis had significantly worse overall survival (OS) (p = 0.007) and cancer-specific survival (CSS) (p = 0.0013). Among all patients, 105 (56.45%) underwent PTR, and this group showed reduced overall mortality (OM) and cancer-specific mortality (CSM) (all p < 0.05). When analyzing different metastatic patterns, PTR significantly lowered the risk of OM and CSM for patients with bone, lung, liver, or distant lymph node (DLN) involvement (all p < 0.05). Additionally, among patients with one or two metastases, those undergoing surgical resection were significantly associated with favorable OS (p = 0.008) and CSS (p = 0.0247). CONCLUSIONS: PTR may confer therapeutic benefits for carefully selected individuals with metastatic MTCs. To integrate these insights into clinical decision-making settings, it is imperative to undertake multicenter prospective studies in the future.

Sugar-sweetened beverage intake and long-term mortality in individuals with metabolic dysfunction-associated steatotic liver disease: a longitudinal analysis of the National Health and Nutrition Examination Survey database.

BACKGROUND: Consuming sugar-sweetened beverages (SSBs) has been linked to the development of various adverse health conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD). This study evaluated associations between SSB intake and long-term mortality among individuals with MASLD using a nationally representative database. METHODS: This population-based, longitudinal study extracted data of adults aged 20-79 years with MASLD from the USA (US) National Health and Nutrition Examination Survey database 2003-2014. Associations between the amount of SSB intake and all-cause, cancer and cardiovascular disease mortality until the end of 2019 were determined using Cox proportional hazards regression analyses. RESULTS: A total of 12 965 individuals aged 20-79 years who had MASLD were identified in the database. After exclusion, 5630 participants remained for the analyses. This cohort can be extrapolated to 43 420 321 individuals in the entire US after proper weighting. The mean age of the study cohort was 44.1 years. After adjusting for confounders, no significant association was observed between SSB intake (tertile 3 vs. tertile 1) and all-cause [adjusted hazard ratio (aHR): 1.03, 95% confidence interval (CI), 0.60-1.76) or cancer mortality (aHR, 0.41; 95% CI, 0.15-1.16). However, higher SSB intake (tertile 3 vs. tertile 1) was significantly associated with elevated cardiovascular disease mortality risk (aHR = 2.83; 95% CI, 1.01-7.91). CONCLUSION: In US adults with MASLD, high SSB intake is associated with nearly three-fold increased cardiovascular disease mortality risk. The findings underscore the critical need for concerted action on the part of healthcare providers and policymakers.

Soft Millirobot Capable of Switching Motion Modes on the Fly for Targeted Drug Delivery in the Oviduct.

Small-scale magnetic robots with fixed magnetizations have limited locomotion modes, restricting their applications in complex environments in vivo. Here we present a morphology-reconfigurable millirobot that can switch the locomotion modes locally by reprogramming its magnetizations during navigation, in response to distinct magnetic field patterns. By continuously switching its locomotion modes between the high-velocity rigid motion and high-adaptability soft actuation, the millirobot efficiently navigates in small lumens with intricate internal structures and complex surface topographies. As demonstrations, the millirobot performs multimodal locomotion including woodlouse-like rolling and flipping, sperm-like rotating, and snake-like gliding to negotiate different terrains, including the unrestricted channel and high platform, narrow channel, and solid-liquid interface, respectively. Finally, we demonstrate the drug delivery capability of the millirobot through the oviduct-mimicking phantom and ex vivo oviduct. The magnetization reprogramming strategy during navigation represents a promising approach for developing self-adaptive robots for performing complex tasks in vivo.

Do antibody CDR loops change conformation upon binding?

Antibodies have increasingly been developed as drugs with over 100 now licensed in the US or EU. During development, it is often necessary to increase or reduce the affinity of an antibody and rational attempts to do so rely on having a structure of the antibody-antigen complex often obtained by modeling. The antigen-binding site consists primarily of six loops known as complementarity-determining regions (CDRs), and an open question has been whether these loops change their conformation when they bind to an antigen. Existing surveys of antibody-antigen complex structures have only examined CDR conformational change in case studies or small-scale surveys. With an increasing number of antibodies where both free and complexed structures have been deposited in the Protein Data Bank, a large-scale survey of CDR conformational change during binding is now possible. To this end, we built a dataset, AbAgDb, that currently includes 177 antibodies with high-quality CDRs, each of which has at least one bound and one unbound structure. We analyzed the conformational change of the Cα backbone of each CDR upon binding and found that, in most cases, the CDRs (other than CDR-H3) show minimal movement, while 70.6% and 87% of CDR-H3s showed global Cα RMSD ≤ 1.0Å and ≤ 2.0Å, respectively. We also compared bound CDR conformations with the conformational space of unbound CDRs and found most of the bound conformations are included in the unbound conformational space. In future, our results will contribute to developing insights into antibodies and new methods for modeling and docking.

Bile acids inhibit ferroptosis sensitivity through activating farnesoid X receptor in gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is associated with high mortality rates. Bile acids (BAs) reflux is a well-known risk factor for GC, but the specific mechanism remains unclear. During GC development in both humans and animals, BAs serve as signaling molecules that induce metabolic reprogramming. This confers additional cancer phenotypes, including ferroptosis sensitivity. Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression. However, it is not fully defined if BAs can influence GC progression by modulating ferroptosis. AIM: To reveal the mechanism of BAs regulation in ferroptosis of GC cells. METHODS: In this study, we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis. We used gain and loss of function assays to examine the impacts of farnesoid X receptor (FXR) and BTB and CNC homology 1 (BACH1) overexpression and knockdown to obtain further insights into the molecular mechanism involved. RESULTS: Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells. This effect correlated with increased glutathione (GSH) concentrations, a reduced GSH to oxidized GSH ratio, and higher GSH peroxidase 4 (GPX4) expression levels. Subsequently, we confirmed that BAs exerted these effects by activating FXR, which markedly increased the expression of GSH synthetase and GPX4. Notably, BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR. Finally, our results suggested that FXR could significantly promote GC cell proliferation, which may be closely related to its anti-ferroptosis effect. CONCLUSION: This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSH-GPX4 axis in GC cells. This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.

Photocatalytic Upgrading of Polylactic Acid Waste into Alanine under Mild Conditions.

Polylactic acid (PLA) has attracted increasing interest as a sustainable plastic because it can be degraded into CO2 and H2O in nature. However, this process is sluggish, and even worse, it is a CO2-emitting and carbon resource waste process. Therefore, it is highly urgent to develop a novel strategy for recycling post-consumer PLA to achieve a circular plastic economy. Herein, we report a one-pot photoreforming route for the efficient and selective amination of PLA waste into value-added alanine using CoP/CdS catalysts under mild conditions. Results show the alanine production rate can reach up to 2.4 mmol gcat -1 h-1, with a high selectivity (>75 %) and excellent stability. Time-resolved transient absorption spectra (TAS) reveal that CoP can rapidly extract photogenerated electrons from CdS to accelerate proton reduction, favoring hole-dominated PLA oxidation to coproduce alanine. This study offers an appealing way for upcycling PLA waste and creates new opportunities for green synthesis of amino acids.

Seasonal assessment of risks to canoeists' health in a Taiwanese recreational river.

Canoeing is the most favorite recreational activity in several Taiwanese rivers. However, river water frequently contains elevated levels of pathogenic Escherichia coli, which has adverse effects on human health. This study adopted a quantitative microbial risk assessment to analyze seasonal risks to canoeists' health in the Dongshan River, Taiwan. First, river E. coli concentrations were statistically analyzed to determine the seasonal distributions. The exposure duration (ED) was determined by field observations. To propagate the parametric uncertainty, Monte Carlo simulation was employed to model the probability distributions of seasonal pathogenic E. coli levels, ingestion rates, and ED for athletes. Finally, the beta-Poisson dose-response model was implemented to determine seasonal health risks for canoeists. The study results indicated that the health risks in infection probability ranged from 0.5 × 10-3 to 8.8 × 10-3 illnesses/person/day for tourists and 1.2 × 10-3 to 7.7 × 10-3 illnesses/person/day for athletes. The health risks in the Lizejian Bridge area for tourists exceeded an acceptable level suggested by the U.S. Environmental Protection Agency, 8 × 10-3 illnesses/person/day, in spring for an ED of 2 h/day, and the health risks for tourists and athletes approached this level in spring and winter for an ED exceeding or equaling 1.5 h/day. According to sensitivity analysis, the geometric standard deviation of river E. coli levels was the most sensitive parameter affecting seasonal risks to canoeists' health. To protect canoeists' health, effluent sewer systems, best management practices, and total maximum daily loads should be promptly implemented in this watershed.

An extracellular matrix-mimicking magnetic microrobot for targeted elimination of circulating cancer cells.

Cancer cells disseminate through the bloodstream, leading to metastasis in distant sites within the body. One promising strategy to prevent metastasis is to eliminate circulating tumor cells. However, this remains challenging due to the lack of an active and targeted biomedical tool for efficient cancer cell elimination. Here, we developed a magnetic microrobot by using natural materials derived from the extracellular matrix (ECM) to mimic the ligand-receptor interaction between cancer cells and the ECM, offering targeted elimination of cancer cells. The ECM-mimicking microrobot is designed with a biodegradable hydrogel matrix, incorporating a cancer cell ligand and magnetic microparticles for cancer cell capture and active locomotion. This microrobot was fabricated based on an interface-shearing method, enabling controllable magnetic response and size scalability (30 µm-500 µm). The presented ECM-mimicking microrobot can actively approach and capture single cancer cells and cell clusters under the control of specific magnetic fields. The experiment was conducted in a blood vessel-mimicking simulator. The microrobot demonstrates an outstanding elimination efficacy of 92.3% on MDA-MB-231 cancer cells and a stable transport capability of the captured cells over long distances to a designed recycling site, inhibiting cell metastasis. This magnetic ECM-mimicking microrobot based on a bioinspired binding mechanism represents a promising candidate for the efficient elimination of cancer cells and other biological waste in the blood.

Survival Benefit of Primary Tumor Resection Combined With Chemotherapy in Patients With Unresectable Colorectal Mucinous Adenocarcinoma With Liver Metastasis.

OBJECTIVE: To evaluate the survival benefit of combining primary tumor resection (PTR) and chemotherapy in patients with unresectable colorectal mucinous adenocarcinoma with liver metastasis (UCR-MAC-LM). METHODS: We obtained data from the surveillance, epidemiology, and end results database for patients with UCR-MAC-LM from 2010 to 2017. Clinicopathological characteristics were analyzed using the χ2 test. Propensity score matching was performed to balance baseline characteristics. Kaplan-Meier analysis and log-rank tests were used to estimate and compare survival outcomes. Univariate and multivariate Cox regression analyses were conducted to identify the prognostic factors. RESULTS: A total of 10,178 patients with unresectable colorectal adenocarcinoma with liver metastasis were included, of whom 6.01% (n=612) had UCR-MAC-LM. The UCR-MAC-LM group had a higher proportion of female patients, a greater number of elderly patients, an increased incidence of right colon localization, larger tumor size, and higher T and N staging than the unresectable colorectal non-mucinous adenocarcinoma with liver metastasis group (P<0.05). Multivariate analysis identified several independent prognostic factors (P<0.05). Patients with unresectable colorectal adenocarcinoma with liver metastasis who underwent PTR+C had superior survival rates compared with those who received PTR/C alone or no treatment (cancer-specific survival, P<0.05; overall survival, P<0.05). Subgroup analysis revealed that 17 of 22 groups of patients with UCR-MAC-LM who received PTR+C had significantly prolonged long-term survival compared with those who received PTR/C alone. CONCLUSIONS: This surveillance, epidemiology, and end results-based study indicates that PTR+C may offer a survival advantage for a specific subgroup of patients with UCR-MAC-LM compared with PTR/C alone. Nonetheless, additional clinical trials are necessary to validate these findings.

Testicular Torsion in Jiaodong Peninsula: A 14-Year Multicenter Retrospective Study.

BACKGROUND: To investigate the correlation between temperature and testicular torsion in Jiaodong Peninsula which has temperate continental monsoon climate and is represented by Yantai and its surrounding areas. METHODS: A retrospective analysis was conducted by reviewing clinical data of 292 patients who were admitted and surgically confirmed to have testicular torsion in the Yantai Yuhuangding hospital medical complex between January 1, 2009, and August 31, 2022. Male patients who underwent circumcision (foreskin) were allocated to the control group. Temperature data were obtained from the China Meteorological Data Service Center. Chi-squared test or Fisher's exact test and one-way analysis of variance were employed to compare patient characteristics and climatic variables among the different groups. Pearson's correlation analysis was used to analyze the association between monthly average ambient temperature and monthly cumulative number of cases. Moreover, a logistic regression model was utilized to identify the independent factors of testicular torsion. RESULTS: The mean age of patients with testicular torsion was 16.8 years. The number of cases was the highest in autumn. The temperature was the highest in summer and the lowest in winter (p < 0.01). Furthermore, the temperature difference (TD) in autumn was the highest in the four seasons groups (p < 0.01). The patients were divided into the high TD and low TD groups according to the mean TD (7.62 ◦C) on the admission day. The high TD group had a higher number of patients than the low TD group, and the temperature was lower in the former group than in the latter group (p < 0.01). A roughly negative correlation was observed between ambient temperature and the number of cases (Pearson's r = -0.228, 95% confidence interval (CI): -0.366 to -0.079, p = 0.003). Logistic regression analysis revealed that the independent risk factor for testicular torsion was TD on admission day (odds ratio, 1.82; 95% CI, 1.28-2.59; p < 0.001). CONCLUSIONS: To some extent, external temperature can affect the body surface temperature of patients and then induce testicular torsion. We concluded that testicular torsion easily occurs in the season in which the temperature drops and the TD is high.